chr10-113697596-C-A

Variant names:

• chr10-113697596-C-A
• rs770345595
• NM_001227.5:c.103C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001227.5(CASP7):​c.103C>A​(p.Leu35Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L35V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CASP7 NM_001227.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62
• Publications: 1 publications found

Genes affected

CASP7 (HGNC:1508): (caspase 7) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. The precursor of the encoded protein is cleaved by caspase 3 and 10, is activated upon cell death stimuli and induces apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07865605).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP7	NM_001227.5	c.103C>A	p.Leu35Ile	missense_variant	Exon 2 of 7	ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.103C>A	p.Leu35Ile	missense_variant	Exon 2 of 7	1	NM_001227.5	ENSP00000358324.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251294 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.019
DANN	Benign	0.78
DEOGEN2	Benign	0.059	T;T;.;T;.;T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.53	T;T;.;.;T;.;.;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.079	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.83	L;.;L;L;L;L;L;.
PhyloP100		-2.6
PROVEAN	Benign	-0.59	.;N;N;N;.;N;N;.
REVEL	Benign	0.029
Sift	Benign	0.33	.;T;T;T;.;T;T;.
Sift4G	Benign	0.43	T;T;T;T;T;T;T;T
Polyphen		0.0010	B;.;B;B;B;B;B;B
Vest4		0.11
MutPred		0.28		Gain of methylation at K38 (P = 0.055);Gain of methylation at K38 (P = 0.055);Gain of methylation at K38 (P = 0.055);Gain of methylation at K38 (P = 0.055);Gain of methylation at K38 (P = 0.055);Gain of methylation at K38 (P = 0.055);Gain of methylation at K38 (P = 0.055);.;
MVP		0.28
ClinPred		0.046	T
GERP RS		-4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.044
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs770345595; hg19: chr10-115457355;